Ali Ahmed, Krista L. Dong, Maryam Hussain, Makhosonke Ngcobo, Ntombifuthi Langa, Ayanda Zulu, Luyanda Maphalala, Vanessa Pillay, Maud Mthembu, Fang Wan, Whitney Tran, Rachel Lau, Jamila K. Stockman, T Ndung’u, Karine Dubé
Analytical treatment interruption (ATI) is a planned and monitored pause of ART used in HIV-related studies that enables measurement of viral rebound kinetics and immune responses, yet it may pose psychological risks to participants. Evidence has largely come from predominantly male cohorts in high-income settings; far less is known about how women living with HIV (WLHIV) in Southern Africa experience ATIs. We conducted a longitudinal sociobehavioral study nested within an ATI-inclusive Phase 2A clinical trial occurring in Durban, South Africa (NCT05281510). Twenty WLHIV who initiated ART during acute HIV and who were enrolled in an ATI clinical trial agreed to participate in this sociobehavioral research study. Participants completed validated psychological assessments at baseline (T1), pre-ATI (T2), post-ATI (T3), and end of clinical trial (T4). Outcomes included decisional certainty, self-esteem, resilience, anxiety, and depression; analyses were descriptive and stratified by time to ART restart: early restart (ER; <16 weeks, n = 6), delayed restart (DR; 16–44 weeks, n = 7), and long-term delayed restart (LTDR; >44 weeks, n = 6). Median decisional certainty increased from T1 4.70 (IQR 0.80) to T4 5.00 (0.00). Self-esteem remained high (T1 24.5; T4 26.0), with the largest gains in the DR group. Resilience was stable (median 4.75–4.50), rising modestly among participants in the LTDR group. Anxiety peaked pre-ATI (T2 33.3 [11.5]) then declined, except in the LTDR group, and anxiety and depression remained high (T4 anxiety 31.0; depression 8.0). ATI was well-tolerated across measures, anxiety spiked only pre-ATI and subsided, except in the LTDR group, where prolonged ATI kept both anxiety and depression elevated. These findings support the inclusion of South African WLHIV in ATI-inclusive clinical trials and highlight the need for psychosocial support for clinical trial participants.